This invention relates to a method for the use of metabolites of secoisolariciresinol diglucoside (SDG) for the treatment of diseases or conditions requiring administration of an antioxidant. These metabolites include secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL).
Reactive oxygen species, which include superoxide anion (O2xe2x88x92), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), have been implicated in the pathophysiology of numerous diseases, including hypercholesterolemic atherosclerosis, diabetes mellitus, ischemic/reperfusion injury, volume or pressure overload heart failure, hemorrhagic shock, endotoxic shock, ageing, inflammatory bowel disease (Crohn""s disease, ulcerative colitis), Parkinson""s disease, rheumatoid arthritis and stroke.
Antioxidants such as vitamin E, secoisolariciresinol diglucoside (SDG), probucol, vitamin C, superoxide dismutase, catalase, sulphasalazine, and various other drugs without antioxidant activity, have been shown to be effective to a varying degree in the diseases referred to above. These drugs, with the exception of vitamin C and E and SDG, are expensive and have adverse side effects.
As described in Prasad, U.S. Pat. No. 5,846,944, incorporated herein by reference, SDG, isolated from flaxseed, has been shown to be effective in lowering cholesterol, and in reducing the development of atherosclerosis in hypercholesterolemic rabbits. It is also effective in reducing the incidence of diabetes mellitus and preventing endotoxic shock.
Reactive oxygen species are known to be involved in the pathophysiology of ageing and numerous diseases, such as hypercholesterolemic atherosclerosis, type I and type II diabetes, ischemic heart disease, heart failure, endotoxic and hemmorhagic shock, inflammatory bowel disease, rheumatoid arthritis, Parkinson""s disease, and stroke.
Secoisolariciresinol diglucoside (SDG), which is obtained from flaxseed, is metabolized to secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL). A description of the above metabolites can be found in a report by R. K. Harris et al. (1991) Methods Development for Phytochemical Compliance Markers in Designer Foods (Flaxseed Powder), Midwest Research Institute. These metabolites are respectively 4.86, 5.02, and 4.35 times more potent than vitamin E, and 3.82, 3.95, and 3.43 times more potent than SDG. Vitamin E, SDG and various other drugs, some with antioxidant activity and some without, are currently used for the treatment of the above diseases.
Drugs presently used to treat the diseases listed above, are expensive and have been less than satisfactory for the treatment of these diseases because of their adverse side effects. The discovery of SDG metabolites offers a safe, less expensive antioxidant that is useful in the treatment of these diseases and conditions. They are derived from dietary flaxseed and are therefore from a natural source, having little to no side effects.
Thus, the present invention relates to the use of secoisolariciresinol (SECO), enterodiol (ED) or enterolactone (EL) for the treatment of diseases or conditions requiring administration of an antioxidant. These diseases or conditions include hypercholesterolemic atherosclerosis, type I and type II diabetes, ischemic heart disease, heart failure, endotoxic and hemmorhagic shock, inflammatory bowel disease, rheumatoid arthritis, Parkinson""s disease, and stroke.
The SECO, ED or EL is preferably used in purified form and can be administered orally or intravenously. It can, for instance, be administered in a once daily oral dosage of about 5-15 mg per kg of body weight. The oral doses may conveniently be in the form of tablets or capsules and these metabolites may be used together with a variety of pharmaceutically acceptable diluents or carriers.
Morbidity and mortality associated with the diseases referred to above and their complications, such as lost wages, increased health costs and social burdens, are enormous. Treatment with the metabolites according to this invention serve to reduce or prevent the late complications associated with these diseases. The morbidity and mortality associated with these diseases is reduced or prevented. This reduces the burden of illness to society, and overall health care costs, and permit these patients to return to the workplace and be productive members of society.